Bone metabolism in thalassemia.
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Adolescent↗
Biomedical subjects
G C Isaia
Publications and source records attributed to G C Isaia.
Bone density and metabolism in thalassaemia.
Twenty-seven thalassaemic patients (13 F, 14 M, aged 8.1-14.9 yr), regularly transfused and chelated with desferrioxamine (30-40 mg/kg/day) were studied. Every patient was submitted to auxological evaluations, dual X-ray absorptiometry to measure bone mineral density (BMD), and to the determination of bone metabolic markers of osteoclastic activity (total urinary hydroxylysylpyridinoline crosslinks, carboxyterminal pyridinoline crosslinked telopeptide of type I collagen [ICTP]) and of osteoblastic activity (bone Gla protein [BGP] and carboxyterminal propeptide of type I procollagen [PIPC]). The evaluations were repeated after 1 year, during which 13 patients continued desferrioxamine chelation while 14 underwent deferiprone chelation (75 mg/kg/day in 3 doses). The data demonstrate widespread bone alterations consisting of osteoporosis, growth failure and bone age delay. Lumber spine (L2-L4) BMD areal values (Z score) inversely correlated with age, as did height SDS of both male and female patients, indicating osteoporosis progressing with age in parallel with growth insufficiency. No clear-cut alterations in bone mineral metabolism were found in basal state and after 1 year. Extensive MR imaging studies are needed to define the contribution of residual bone marrow hyperplasia to thalassaemic osteopathy suggested by subtle radiological signs as enlargement of bone marrow cavities with thinning of the cortical bone and abnormalities of the trabecules of spongy bone.
Absorptiometry, Photon↗
Ipriflavone prevents radial bone loss in postmenopausal women with low bone mass over 2 years.
Two hundred and fifty-five postmenopausal women with distal forearm bone mineral density (BMD) 1 SD below the mean value for normal age-matched postmenopausal subjects were randomly allocated to a 2-year treatment with oral ipriflavone (200 mg t.i.d) or a matched placebo, according to a double-masked, parallel group design. All patients also received a 1 g/day calcium supplement. Distal radius BMD and bone metabolism markers were measured at baseline, and every 6 months. Blood haematology and chemistry and physical parameters were monitored at the same time. One hundred and ninety-six patients completed 2 years of treatment. BMD changes from baseline were analysed according to valid completers (VC) and intention to treat (ITT) analyses. In both cases radial BMD was maintained in patients treated with ipriflavone while in decrease in those receiving the placebo, the between-treatment difference being significant at year 1 and year 2. Urinary hydroxyproline/creatinine levels were decreased in the ipriflavone-treated group and increased in the placebo group, with a significant between-treatment difference. Adverse reactions, mainly gastrointestinal, occurred to a similar extent in the two treatment groups.
Aged↗
Senile osteoporosis: pathophysiology and therapeutic perspectives.
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Aged↗
Effect of chronic treatment with ipriflavone in postmenopausal women with low bone mass.
We present the results of two multicenter, double-blind, placebo-controlled, 2-year studies to evaluate the efficacy and tolerability of ipriflavone in postmenopausal women (PMW) with low bone mass. 453 PMW (aged 50-65 years) with a vertebral (VMD) or radial (RMD) mineral density value 1 SD lower compared with age-matched controls, were randomly selected to receive oral ipriflavone (200 mg T.I.D. at meals) or matching placebo, plus 1 g oral calcium daily. Vertebral (study A, by dual X-ray absorptiometry-DXA) and radial (study B, by dual photon absorptiometry-DPA) bone density, serum bone Gla-protein (BGP), and urinary hydroxyproline/creatinine (HOP/Cr) were measured every 6 months. In both studies, the Valid Completers (VC) analysis showed a maintenance of bone mass in ipriflavone-treated women, whereas in the placebo group, bone mineral density (BMD) was significantly decreased. The final outcome was a bone-sparing effect of 1.6% in study A, and of 3.5% in study B after 2 years. The Intention to Treat (ITT) analysis confirmed the decrease in the placebo group, with no changes in ipriflavone-treated women. A significant (P < 0.05) between-treatment difference was found in both studies. Biochemical markers of bone turnover decreased in patients treated with ipriflavone, thus suggesting a reduction of bone turnover rate. Twenty-six women treated with ipriflavone and 28 receiving the placebo dropped out because of side effects, mainly gastrointestinal. The compliance to the oral long-term treatment was good. The results of these studies show that ipriflavone is able to prevent both axial and peripheral bone loss in PMW with low bone mass, and is well tolerated.
Absorptiometry, Photon↗
Densitometric study of developing vertebral bodies.
To define the quantitative aspects of ossification of human fetal spine, we performed a high resolution densitometric study by lateral and postero-anterior scanning of five fetal spines (18-36 weeks of conceptual age) and one spine of a 4-month-old infant. The data were plotted against developmental age for each spine and vertebra. Bone mineral content increased with developmental age, with a peak at the upper lumbar level, in agreement with the ossification pattern of the spine, reported in embryological literature. Bone mineral density (BMD) was unrelated to developmental age, and showed similar trends for each vertebra in all the vertebral columns examined. The changes of BMD seems to be a phenomenon related to individual variability. This study also demonstrates that densitometric techniques may provide useful and interesting information in studies on skeletal development.
Absorptiometry, Photon↗
[Synthetic salmon calcitonin suppositories for the short-term treatment of involutive osteoporosis].
Intramuscular and intranasal synthetic salmon calcitonin (sCT) has long been used in the treatment of involutional osteoporosis. A new suppository formulation was developed and many studies demonstrated that rectally administered sCT is efficacious and well tolerated. Thirty postmenopausal women, who had a bone mineral density at the lumbar spine below the mean of age-matched women, were enrolled in this study. Using an open balanced, randomized design, the patients were allocated to two groups of treatment: sCT suppositories at the dose of 100 UI/day or 200 UI every other day for six months. Treatment with sCT suppositories caused a statistically significant decrease of pain in both study groups. Bone mineral density at lumbar spine showed an increase in both study groups with significant difference respect the basal value for the patients treated with sCT on alternate day. Based on the results of this study, we can thus conclude that sCT in suppository formulation is effective in reducing pain sintomatology, bone loss and turnover in involutional osteoporosis.
Aged↗
Alpha-melanocyte-stimulating hormone antagonizes the inhibitory effect of corticotropin-releasing hormone on luteinizing hormone secretion during the luteal phase in normal women.
CRH inhibits the secretion of gonadotropins by activating endogenous opioids, whereas alpha MSH, which displays various behavioral and neuroendocrine effects contrary to those of the opioids, stimulates their release. To evaluate the possible interaction of CRH and alpha MSH, eight women in the luteal phase underwent the following tests: 1) ovine CRH infused at 100 micrograms/h for 3 h, 2) alpha MSH (2.5 mg as an iv bolus 60 min after the start of saline infusion), 3) CRH plus alpha MSH (injected 60 min after the start of CRH infusion), and 4) placebo. LH, FSH, PRL, ACTH, and cortisol were determined every 15 min for 180 min. CRH significantly (P < 0.001) reduced serum LH. alpha MSH alone significantly (P < 0.001) increased LH to a peak within 15-30 min (baseline, 3.3 +/- 0.7 mIU/mL; maximum increase, 3.5 +/- 0.9 mIU/mL) and induced an even greater rise when injected during the CRH infusion (baseline, 2.8 +/- 03 mIU/mL; maximum increase 7.5 +/- 1.6 mIU/mL; P < 0.05 vs. alpha MSH alone). FSH was always unaffected. ACTH and cortisol increased (P < 0.001) during the CRH infusion and fell significantly (P < 0.001) during the placebo infusion. alpha MSH had no effect on these changes. PRL fell during the placebo infusion (P < 0.001). No changes were induced by CRH or alpha MSH. In conclusion, alpha MSH antagonizes CRH inhibition of LH secretion. This finding lends support to the view that differential posttranslational processing of POMC contributes to the regulation of LH secretion. Further investigation is needed to clarify the mechanism of the antagonism between alpha MSH and CRH.
Adrenocorticotropic Hormone↗
Influence of estrogens on calcitonin secretion.
In this study we investigated the calcitonin (CT) pattern both in basal conditions and after calcium infusion before and one month after oophorectomy in 17 premenopausal women. In addition, 13 oophorectomized women were randomly allocated to two groups, one given hormone replacement treatment and the other untreated, and CT response to hypercalcemia was reevaluated one year later. CT response to calcium infusion was significant only before oophorectomy and one year after estrogen-progestogen treatment, whereas there was no response one month after oophorectomy or after one year without hormone replacement therapy. Our data indicate that both estrogen secretion and replacement treatment may be important factors in CT response.
Adult↗
Effects of ipriflavone on bone mass and calcium metabolism in postmenopausal osteoporosis.
Recently it has been demonstrated that ipriflavone (IP), an isoflavone derivative, is able to increase bone mass in patients with established postmenopausal osteoporosis (PMO). Here we present a preliminary report of a 2-year multicenter, double-blind, placebo-controlled clinical study performed in order to evaluate the efficacy and tolerability of IP in PMO. A large number of patients with PMO, referred to 12 Italian centers, was randomly divided into 2 groups and treated with oral IP (600 mg/day) or placebo (Pl). All patients received an oral Ca supplement (1 g/day). One hundred and twenty six patients completed 1 year of the study. Bone mineral density (BMD) of the distal radius, measured by DPA, serum osteocalcin (BGP), and urinary hydroxyproline excretion (HOP/Cr), were measured before and after 12 months. After 12 months, a significant increase in BMD was observed in the IP-treated group (P < 0.05). IP determined a reduction of HOP/Cr, while in Pl-treated patients a significant increase of this index, as well as of BGP, was observed. After 12 months the difference between the two groups resulted significant (P < 0.05) for BGP. The drug was well tolerated and the patients' compliance to the oral treatment resulted excellent. The results of this study indicate that IP is able to increase bone mass in patients with PMO.
Aged↗
Vertebral bone loss in menopause.
A direct correlation between loss of ovarian function and reduction of bone mass is well established. The incidence of fractures sharply increases with age starting from the menopause. Therefore, it is very important to know the rate of bone loss occurring after menopause, at both trabecular and cortical levels. Several factors may contribute to the reduction of bone mass in menopause. Reduced estrogen secretion results in reduced intestinal calcium absorption, increased bone resorption, and probably a deficient production of calcitonin. Furthermore, in vivo and in vitro experimental data confirm that estrogen failure is associated with histologic changes, mirroring the biochemical changes described in postmenopausal osteoporosis.
Aged↗
[Effect on phospho-calcium metabolism of testosterone administration in hypogonadal males].
Many authors have shown that osteoporosis is an important complication in male hypogonadism, due to the chronic lack of androgens; but in hypogonadal males the pathogenesis of osteopenia isn't completely explained. In this work we examined in 10 hypogonadal males (4 with Klinefelter's Syndrome and 6 with Hypogonadotropic Hypogonadism) lumbar bone mineral content (BMC) and the effects of testosterone (Sustanon) administration on BMC and other phosphocalcium parameters. We evidenced lower BMC levels in hypogonadal subjects if compared to those observed in the control age-matched group; moreover after 3 months of treatment a statistically significant increment of plasma bone gla protein, calcitonin and lumbar BMC was observed. On the contrary no significant variation was observed in osteoclastic indexes (PTH-MM, OHPU/CrU, CaU/CrU) after treatment. In addition both calcitonin basal levels and secretory reserve, measured with calcium infusion, were significantly increased after treatment. Our data confirm the hypothesis that androgen acts on bone principally directly at osteoblastic level, in a stimulatory manner, and indirectly, with calcitonin mediation, with inhibition of osteoclasts.
Adolescent↗
Mineralometry of the lumbar spine and histomorphometry of the iliac crest: preliminary results of a comparison of several parameters in the same individual.
Twelve patients affected with various bone pathologies (osteoporosis, renal osteodystrophy, osteogenesis imperfecta, hyperparathyroidism) were submitted to mineralometry of the lumbar spine with double photonic ray and transiliac biopsy for histomorphometry. A comparison of the values obtained for the mineralometric and histomorphometric parameters--despite the small number of cases--revealed a correlation between bone mineral content of the lumbar spine and trabecular and cortical bone volume of the iliac crest. The correlation is even more significant for the sum of these last two parameters. It may be concluded that: 1) both the methods have predictive values for an evaluation of osteopenia; 2) the measurement of cortical and subcortical bone volume increases the significance of the histomorphometric finding (which is usually limited to the trabecular bone volume); 3) there is a correlation between histomorphometry (iliac crest bone volume) and mineralometry (lumbar spine with double photonic ray) in the same individual.
Absorptiometry, Photon↗
Vertebral bone density in non-amenorrhoeic hyperprolactinaemic women.
Recently, a decrease in bone mineral content (BMC) in hyperprolactinaemic women with long-lasting amenorrhoea has been reported, and attributed either to a direct effect of PRL on bone or secondary to the oestrogen deficiency. To verify if PRL by itself has a direct effect on bone, we have studied BMC at the lumbar level by double-photon absorptiometry in 22 patients with hyperprolactinaemia, selected on the basis of normal or near-normal oestradiol levels. The results were compared with those obtained in 28 healthy closely-matched women, and seven hyperprolactinaemic patients with long-lasting amenorrhoea and oestrogen deficiency. No significant difference in BMC was observed between hyperprolactinaemic patients with normal oestrogen levels (mean +/- SEM = 3.87 +/- 0.10 gHA/cm) and normal subjects (mean +/- SEM = 3.76 +/- 0.10 gHA/cm). Moreover, no significant change was observed during a 6 month follow-up in 13 patients. On the other hand, a significant difference (P less than 0.05) was detected in BMC between the hyperprolactinaemic patients with normal oestradiol levels and those with long-lasting amenorrhoea and oestrogen deficiency (mean +/- SEM = 3.39 +/- 0.18). These results suggest that hyperprolactinaemia by itself is not a risk factor for the development of osteoporosis.
Adult↗
[Ultrasonic evaluation of primary hyperparathyroidism].
The authors evaluated the diagnostic reliability of echotomography in detecting parathyroid masses: 37 patients were studied with primary hyperparathyroidism, in four cases recurrent. They all underwent surgical ablation of the mass, identification of all glands, and biopsy of an apparently normal parathyroid. Echotomography was accurate in 91.4% of cases: it identified 27 out of 39 pathological glands (sensibility 69.2%) and gave no false-positive results (specificity 100%). Since parathyroid is often ectopic, oblique scans are suggested, i.e. of jugulum while the patient is swallowing. Such scans were always used in our study, in order to identify lesions even in case of "difficult" locations, such as the superior mediastinum.
Adenoma↗
[Recent diagnostic and therapeutic findings on postmenopausal and senile osteoporosis].
The incidence of osteoporosis in the West is considerable and its complications are such as to make it a common and disabling problem. Recent developments in the classification, pathogenesis and diagnosis of the disease are reported. Certain laboratory techniques have recently been developed that can provide adequate information about the degree of demineralisation present. Furthermore the accurate in vivo assessment of bone density is made possible by the development of double beam photon osteodensitometry that measures bone mineral content (BMC) with sensitivity and accuracy. On the treatment side, the various drugs available are reviewed with particular reference to estrogen, vitamin D, anabolisers (recently reassessed in radiogrammometric and densitometric studies) fluorides and calcitonin. Finally certain treatment protocols for post-menopausal and senile osteoporosis are proposed that should produce good results in a reasonably short space of time.
Aged↗
[Prolactin, a marker of essential headache?].
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Female↗
Results of long term treatment of advanced prostatic cancer with the LHRH analogue buserelin.
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Buserelin↗